Artificial pyramid

ABSTRACT

Disclosed is an artificial vertebra having a bone-marrow regenerating function, comprising a hydroxyapatite (HAp)/collagen (Col) composite body formed by pressure-dehydrating a coprecipitate of hydroxyapatite and collagen to have a nanocomposite structure in which HAp particles are conjugated along a Col fiber while aligned each of the c-axes of the HAp particles along the Col fiber. The HAp/Col composite body is formed with a perforated aperture for allowing a blood vessel and an osteogenic cell to intrude thereinto. The present invention also provides a biodecomposable/bioabsorbable support for fixing an artificial vertebra, comprising a polylactic acid plate prepared by injection-molding molten polylactic acid and then extrusion-molding the injection-molded polylactic acid in such a manner that it is draw-oriented in a uniaxial direction. The plate has four corner regions each formed with a screw hole for fixing the plate to vertebral bodies.

TECHNICAL FIELD

[0001] The present invention relates to an artificial vertebra. Inparticular, the present invention relates to an artificial vertebrahaving a bone-marrow regenerating function which is achieved by using ahydroxyapatite/collagen (HAp/Col) composite material capable ofself-organizing after filled in a bone defect area of a vertebral bodyin anterior fusion of the spine, and a support composed of apolylactic-acid (poly-L-lactide: PLLA) plate suitable for fixing theartificial vertebra to the vertebral body.

BACKGROUND ART

[0002] Generally, if an artificial material is implanted to fill a bonedefect area in a living body, it will be wrapped by a fibrous membrane,and finally isolated from surrounding tissues. This phenomenon is causedby a biological reaction for self-protecting from foreign matters.Exceptionally, some materials can be joined directly to a surroundingbone without any formation of fibrous membranes. A typical materialhaving such a property includes hydroxyapatite Ca₁₀(PO₄)₆(OH)₂ andtricalcium phosphate Ca₃(PO₄)₂.

[0003] Recently, an artificial bone made of an organic/inorganiccomposite material based on the above bioceramics is being developed.For example, Japanese Patent Laid-Open Publication No. H07-101708discloses an implant for artificial bones or artificial tooth roots,which is formed as a molded piece by adding 5 to 40 weight % of water toa composition powder containing an apatite powder having a crystal grainsize of 0.5 μm or less and a biomolecular organic matter such ascollagen and applying a pressure of 50 MPa or more to the compositionpowder maintained at a temperature of 0 to 200° C., wherein the Young'smodulus of the implant is adjustable in the range of 2 GPa to 110 MPa.

[0004] The inventors developed an oriented apatite/collagen compositematerial excellent in flexural strength, Young's modulus and compressivestrength suitable as a biomedical bone-replaceable bone-reconstructionmaterial having a bone-induction ability and a bone-conduction ability,through a method in which a phosphoric-acid solution containing collagenand a solution containing calcium salt are simultaneously dropped into areaction vessel to coprecipitate calcium phosphate and collagen, and theobtained precipitate is shaped under pressure (Japanese Patent Laid-OpenPublication No. H11-199209, J. BIOMEDICALS RESEARCH, 54: 445-453,Published online, 4 Dec. 2000).

[0005] Japanese Patent Laid-Open Publication No. H08-336584 discloses anapatite porous body for artificial bone marrows, which includes 30weight % or more of apatite crystal particles having a particle size of2 nm to 0.2 μm and an organic matter such as collagen, and has athrough-hole with a diameter of 10 μm to 2 mm. Japanese Patent Laid-OpenPublication No. H07-88174 discloses a compression-molded osteogenicimplant comprising rhBPM (Bone Morphogenetic Protein) and a carriertherefor, wherein the osteogenic implant is formed in a support made ofa bioceramics material.

[0006] As a substitute for a conventional bone-connecting metal plate orscrew which has been generally used to fix, aid and restore a brokenbone, a fusion-molded or extrusion-molded body made of polylactic acidas a biodecomposable/bioabsorbable material and formed in a rod, plate,screw or pin shape (Japanese Patent Laid-Open Publication Nos. H03-29663and H05-168647).

[0007] While an autologous bone has been extracted and used as animplant for filling a bone defect area of a vertebral body in manycases, various kinds of artificial implants made of metal or ceramichave also been developed.

[0008] Since a vertical load is imposed on an artificial implant duringuse, the artificial implant must adequately satisfy requirements offlexural strength, flexural modulus and compressive strength, and havecharacteristics equivalent to those of an autologous bone.

[0009] For example, Japanese Patent Laid-Open Publication No. H04-303444(Publication-1) discloses an artificial intervertebral disk in blockform having various shapes. The artificial intervertebral disk comprisesa plurality of porous bodies made of metal or ceramic, and a block madeof polyvinyl alcohol hydrogel and integrally disposed between the porousbodies.

[0010] The specification and drawings of U.S. Pat. No. 5,702,449(Publication-2) discloses an artificial vertebra comprising a loadsupport member composed of a cylindrical metal sleeve with a sidewallhaving a number of apertures, and a bioceramic, such ashydroxyapatite/tricalcium phosphate, received in the inner space of thesupport member.

[0011] Japanese Patent Laid-Open Publication No. H10-33656(Publication-3) discloses a vertebral-body fusion member in block formhaving various shapes. The vertebral-body fusion member comprises aporous body and a dense body having a mechanical strength which are madeof β-tricalcium phosphate (TCP) as a bioabsorbable material having abone-conduction ability, wherein the porous and dense bodies areintegrally combined so that the dense body maintains an initialstrength, and the porous body is gradually transformed into anautologous bone.

[0012] Japanese Patent Laid-Open Publication No. H11-513590(Publication-4) discloses a porous biodecomposable matrix for bonereplacement in spinal fusion, filling of bone defects, repair of brokenbones or filling of periodontal defects. The matrix includes a networkof insoluble biopolymer fiber (fibril collagen), binder, and fixedcalcium phosphate mineral (hydroxyapatite) which are linked together.Publication-4 also discloses that it is desired to arrange the weightratio of collagen to calcium phosphate mineral in the range of 8:2 to1:1, to cross-link the matrix with glutalaldehyde or the like, and toinclude a bone marrow cell, an autologous bone and a bone growth factor.

[0013] Published Japanese Translation of PCT International Publicationfor Patent Application No. 2000-507484 (Publication-5) discloses avertebral-column spacer comprising a load support member which includesa bone implant having a bioceramics matrix and a bone-growth stimulatingcomponent impregnated in the bioceramics matrix

[0014] Published Japanese Translation of PCT International Publicationfor Patent Application No. 2000-508221 (Publication-6) discloses acylindrical implant comprising a matrix body which has fine pores andincludes a biphasic calcium phosphate ceramic containing 2 to 40 volume% of hydroxyapatite (HAp) and 98 to 60 volume % of tricalcium phosphate(TCp), and a bone-growth inducing factor (TGF-β, BMP, prostaglandinetc.) captured in the matrix body. Publication-6 also discloses that theceramic has fine pores with a size of about 200 to 600 μm, and theporosity rate of the ceramic is in the range of about 60 to 80%.

[0015] Published Japanese Translation of PCT International Publicationfor Patent Application No. 2000-517221 (Publication-7) discloses aprismatic or cylindrical intervertebral implant made of a conventionalceramic material having a maximum porosity of 30 volume %, wherein eachof pores with a diameter of less than 100 μm is filled with air.Publication-7 also discloses that the intervertebral implant has acompressive strength of 400 to 600 MPa, and the ceramic material istransparent to X-ray.

[0016] The block disclosed in Publication-1 is simply implanted in acortical bone, but no bone-marrow structure will be formed. Theartificial vertebra disclosed in Publication-2 has a problem of causingrupture on the boundary between the bone and the implant underrepetitive stress due to remanence of the metal sleeve which originallyhas no potential of becoming bone. Further, there is the risk of causingdisruption of the implant itself due to early absorption/deprivation ofTCP, and poor bone conduction ability provided only by HA left at thecentral region of the sleeve.

[0017] Publication-3 simply discloses that the dense body is combinedwith the porous body to compensate for a poor strength of β-tricalciumphosphate (TCP). The matrix disclosed in Publication-4 simply includes amixture of collagen and apatite, which has neither a bone-likenanocomposite structure nor a self-organizing function. In addition, thematrix is insufficient in strength and bone-forming ability.

[0018] The matrix itself of the spacer disclosed in Publication-5 has noability of forming bone marrow. The spacer also involves a conventionalproblem such as complications in a bone-extraction area and metalfatigue, due to use of an autologous bone and a metal component.Further, allogeneic bone transplantation involves the risk of AIDS orhepatitis infection. While the porous body disclosed in Publication-6 ismade of a TCP-HAp composite material, it has no self-organizingfunction. Further, the implant itself is not a carrier directlyabsorbing BMP. While the porous body disclosed in Publication-7 has ahigh porosity, it involves the risk of rupture under repetitive stressdue to insufficient transformation into an autologous bone. Further, anyvertebra structure cannot be biologically formed without using abone-marrow implant.

[0019] As mentioned above, each of the conventional artificial vertebraeis not a bioabsorbable material having abilities of bone-marrowformation and self-organization (bone-tissue regeneration).

DISCLOSURE OF THE INVENTION

[0020] It is therefore an object of the present invention to provide anartificial vertebra with a 3-dimensional structure, having amicrostructure (nanocomposite structure) and composition equivalent tothose of an autologous bone, and exhibiting excellent characteristicssuch as invasivity of new blood vessels, osteogenic cells and others.

[0021] The inventors developed a HAp/Col composite material excellent inbone-conduction ability, as disclosed in the aforementioned JapanesePatent Laid-Open Publication No. H11-199209, J. BIOMEDICALS RESEARCH,54: 445-453, Published online, 4 Dec. 2000. Then, through researches onapplication of the composite to artificial vertebrae, the inventors hasfound a 3-dimensional structure of an artificial vertebra having abone-marrow regeneration ability which is achieved by using a HAp/Colcomposite material, and developed a biodecomposable/bioabsorbablesupport suitable for use with the artificial vertebra to fix it to avertebral body.

[0022] The artificial vertebra of the present invention is made of abioabsorbable material which has an adequate strength capable ofwithstanding an initial load, or a load to be applied in the early stageafter implantation, and excellent abilities of bone conduction, celldifferentiation/proliferation, bone-marrow formation andself-organization (bone-tissue regeneration), and exhibits excellentcharacteristics equivalent to an autologous bone.

[0023] Specifically, the present invention provides an artificialvertebra having a bone-marrow regenerating function, comprising ahydroxyapatite (HAp)/collagen (Col) composite body formed bypressure-dehydrating a coprecipitate of hydroxyapatite and collagen tohave a nanocomposite structure in which HAp particles are conjugatedalong a Col fiber while aligned each of the c-axes of the HAp particlesalong the Col fiber. The HAp/Col composite body is formed with aperforated aperture for allowing a blood vessel and an osteogenic cellto intrude thereinto.

[0024] In the artificial vertebra of the present invention, the weightratio of HAp to Col in the HAp/Col composite body may be in the range of70:30 to 80:20 which is equivalent to that of a bone. If HAp isexcessively included beyond this range, the HAp/Col composite bodybecomes brittle due to increased Young's modulus. If Col is excessivelyincluded beyond the above range, the HAp/Col composite body will havedeteriorated strength.

[0025] The coprecipitate may have a cross-linked surface.

[0026] The HAp/Col composite body may be formed as a block having ahorseshoe shape in a section orthogonal to the long axis thereof. Inthis case, a portion of the block to be located frontward relative tothe front side of a human body may have a curved surface having ananalogous shape to that of a vertebral body, and a portion of the blockto be inserted into vertebral bodies may have rectangular planersurfaces to provide an increased contact area with the vertebral bodies.

[0027] The aperture may be perforated in the direction of the long axisof the HAp/Col composite body in a configuration analogous to that of aHaversian canal. In this case, a plural number of the apertures arearranged at even intervals.

[0028] The aperture may also be perforated in the frontward/rearwarddirection and rightward/leftward direction relative to the front side ofa human body in a configuration analogous to that of a Volkmann's canal.In this case, a plural number of the apertures are arranged at evenintervals.

[0029] The HAp/Col composite body may be adapted to receive a load in anearly stage after implantation. In this case, the HAp/Col composite bodyhas a function of being transformed into an autologous bone in such amanner that new bone (bone marrow) is initially formed in the perforatedaperture and the transformation is then extended from the new boneregion to the periphery thereof.

[0030] The artificial vertebra of the present invention may include anosteogenic factor impregnated into the HAp/Col composite body.

[0031] The present invention also provides abiodecomposable/bioabsorbable support for fixing an artificial vertebra,comprising a polylactic acid plate prepared by injection-molding moltenpolylactic acid and then extrusion-molding said injection-moldedpolylactic acid in such a manner that it is draw-oriented in a uniaxialdirection, wherein the plate has four corner regions each formed with ascrew hole for fixing the plate to vertebral bodies.

[0032] The screw hole may be perforated in an oblique direction.

[0033] Further, the present invention provides an artificial vertebraassembly comprising in combination the above artificial vertebra and theabove biodecomposable/bioabsorbable support.

[0034] A cortical bone has an extremely high hardness. In big animals,the cortical bone is composed of a number of lamellas. Blood vessels andnerves are distributed within the cortical bone, specifically, in aHaversian canal extending along the center of the concentric lamellasand a perforating canal (Volkmann's canal) extending transverselythrough the lamellas.

[0035] The artificial vertebra of the present invention comprises theHAp/Col composite body formed with perforated apertures analogous to theHaversian canal and the Volkmann's canal. The characteristics of theHAp/Col composite body and the perforated apertures allows blood vesselsand osteogenic cells to readily intrude in the inside of the artificialvertebra after implantation, to form a structure equivalent to that of anatural bone having a cancellous bone (bone marrow) in the centralregion thereof and a cortical bone (HAp/Col) surrounding the cancellousbone.

[0036] The plurality of Volkmann's canal-like apertures perforated inthe frontward/rearward direction and rightward/leftward direction of theblock relative to the front side of a human body have a function ofallowing blood vessels to intrude from the periosteum of a vertebralbody into the block together with osteogenic cells. Preferably, theaperture has a diameter of about 0.4 to 0.6 mm.

[0037] If the diameter is greater than 0.6 mm, the block is liable tocause cracks. If the diameter is less than 0.4 mm, the amount of newbone formation will be reduced, and consequently the transformation ofthe HAp/Col composite body to an autologous bone will be undesirablydelayed.

[0038] The Haversian canal-like aperture perforated in the directions ofthe long axis of the block has a function of allowing blood vessels tointrude from the periosteum of a vertebral body into the block togetherwith osteogenic cells. Preferably, the aperture has a diameter of about0.4 to 0.6 mm. If the diameter is greater than 0.6 mm, the block isliable to cause cracks. If the diameter is less than 0.4 mm, the amountof new bone formation will be reduced, and consequently thetransformation of the HAp/Col composite body to an autologous bone willbe undesirably delayed.

[0039] In the artificial vertebra of the present invention, the HAp/Colcomposite body has a characteristic capable of allowing the above smallaperture to be perforated therein with a driller or the like, andmaintaining adequate flexural strength, compressive strength and Young'smodulus required as an artificial vertebra even if a number of theapertures are perforated therein.

[0040] In use of the artificial vertebra of the present invention, theblock is inserted into a space formed by cutting a specific vertebralbody while pulling a pair of vertebral bodies located on the upper andlower sides of the specific vertebral body upward and downward to allowthe upper and lower surfaces of the block to be interposed or clampedbetween the upper and lower vertebral body. Thus, the block or theHAp/Col composite body can receive a vertical initial load by itself asa substitute for a cortical bone, and the perforated apertures caninduce the intrusion of blood vessels and osteogenic cells. If theHAp/Col is impregnated with rhBMP, bone formation will be facilitated toprovide an enhanced initial strength after implantation. Over the years,the HAp/Col composite body will be transformed into an autologous bonein such a manner that new bone (bone marrow) is initially formed in eachof the perforated apertures and the transformation is then extended fromthe new bone region to the periphery thereof.

[0041] The artificial vertebra of the present invention has thefollowing features:

[0042] (1) After implantation, the artificial vertebra is transformed tohave a structure comprising a bone marrow (new bone created in theHaversian canal-like and Volkmann's canal-like perforated apertures) anda cortical bone (bone formed by the HAp/Col composite body and the BMPimpregnated therein, which is equivalent to a natural bone (naturalvertebral body);

[0043] (2) A bone-remodeling unit is formed in the HAp/Col compositebody corresponding to a cortical bone forms, to allow the HAp/Colcomposite body to be transformed into an autologous bone or toself-organize; and

[0044] (3) The BMP can be absorbed directly into the HAp/Col compositebody without using any other carrier.

[0045] There has not been known any artificial material capable offorming a bone-remodeling unit therein, and thus the artificial vertebraof the present invention is a novel biomedical material having abone-conduction ability equivalent to that of an allogeneic bone.

[0046] In the present invention, the polylactic acid (PLLA) plate foruse in fixing the above artificial vertebra has a mechanicalcharacteristic and configuration suitable for anterior fusion of thecervical spine.

[0047] In view of the chemical composition, a bone is made of “proteinconsisting of collagen” and “inorganic crystal analogous tohydroxyapatite”. The weight ratio of the protein to the inorganiccrystal is about 3:7. The two materials are characteristically arrangedin order even in the nano range. The collagen has a size of 300 nm, andthe apatite crystal has a size of 50 nm. Thus, it can be said that abone is a typical organic/inorganic nanocomposite.

[0048] A bone is regenerated by an osteoblast, and absorbed by anosteoclast. The metabolism of calcium and phosphorous in a lining bodyis widely associated with bone formation. However, in a local viewpoint,an osteoblast first synthesizes collagen, and extracellularly releasesthe collagen to form an organic skeleton. Then, a small apatite crystalis formed, and a bone will be developed. As above, a bone is anextracellular matrix in which apatite and collagen are autonomouslyconjugated together in a local space around the osteoblast. Thus, it isexpected that apatite and collagen are self-organizingly conjugatedtogether by duplicating a chemical circumstance analogous to the localspace around the osteoblast.

[0049] A HAp/Col composite as a material of the artificial vertebra ofthe present invention is synthesized by simultaneously dropping acalcium-hydroxide suspension and a phosphoric-acid solution containingcollagen into distilled water to form a coprecipitate, andpressure-dehydrating and shaping the obtained coprecipitate. During thecoprecipitation or after the shaping of the coprecipitate, the surfaceof the coprecipitate may be cross-linked through a chemicalcross-linking method using glutalaldehyde, or any other suitablecross-linking method such as a thermal cross-linking method or anultraviolet cross-linking method, to provide an enhanced initialstrength.

[0050] The HAp/Col composite synthesized through the above process has ananocomposite structure analogous to that of a bone, in which HApcrystals are conjugated along a Col fiber while aligned each of thec-axes of the HAp particles along the Col fiber. Thus, when the HAp/Colcomposite body is implanted in a living body, it will be transformedinto an autologous bone in a similar process to that of a natural bone.FIG. 4 is a TEM image and an electron diffraction image of the HAp/Colcomposite body. The images show HAp crystals arranged along a collagenfiber. The arrow in the electron diffraction image indicates the c-axisorientation of the HAp crystal.

[0051] In the artificial vertebra of the present invention, the HAp/Colcomposite body has a compressive strength capable of withstanding a loadin an early stage after implantation. While the HAp/Col composite bodyis a bulk material, the surface of the HAp/Col composite body will begradually decomposed and absorbed in vertebral bodies in contacttherewith under load in a living body. In response to the absorption,macrophages are mobilized to treat the decomposition product, so thatthe decomposition product is differentiated into osteoclasts in thevertebral bodies. Further, the decomposition product attracts theosteoclasts, and the osteoclasts induce osteoblasts to form new bone soas to provide excellent bone conduction ability. Differently fromhydroxyapatite, AW glass or lactic-acid-based polymer, the HAp/Colcomposite body in the artificial vertebra of the present invention istransformed into real bone in a living body.

[0052] If the HAp/Col composite body is not cross-linked, it will beabsorbed by an osteoclast-like multinucleate to form a structure (pitsor depressions) analogous to Howship's lacunae. It can be observed thatosteoblasts positively form new bone around the structure. Thus, it isbelieved that the HAp/Col composite body in the artificial vertebra ofthe present invention can be incorporated into abone-regeneration/absorption metabolism (remodeling cycle) to form newbone.

[0053] Any cross-linking treatment has no negative affect on thebiocompatibility of the HAp/Col composite body. The cross-linkingtreatment provides an extended time-period allowing the HAp/Colcomposite body to be absorbed in a lining body. The cross-linkingtreatment has no affect on the function of allowing tissues to intrudein the perforated aperture, and thus the bone-conduction ability isadequately maintained. If the degree of cross-linking is increased,deterioration in cell activity will be observed. The cell activity wouldbe deteriorated by reason that the decomposition of collagenase is notadequately developed due to the cross-linking, and consequently theabsorption of the decomposition product by cells is delayed.

[0054] Both collagen and hydroxyapatite have a high affinity withprotein, and the hydroxyapatite of the HAp/Col composite body used inthe artificial vertebra of the present invention is a microcrystal.Thus, the HAp/Col composite body has an effective area for absorbingprotein, incomparably lager than that of the conventional material usinghydroxyapatite, and serves as an excellent carrier of an osteogenicfactor such as rhBMP. The impregnation of the osteogenic factor such asrhBMP facilitates bone formation in the entire peripheral surface of theartificial vertebra to allow a load to be imposed on the artificialvertebra in earlier stage after implantation. In addition, theartificial vertebra is quickly integrated with the natural vertebrabodies. Thus, the artificial vertebra of the present invention can beused to achieve desirably reduced treatment period.

[0055] The artificial-vertebra fixing support of the present inventioncomprising a polylactic acid (PLLA) plate may be produced by forming aflat plate with molten polylactic acid through injection molding,setting the flat plate in a vessel of an extrusion machine, and forcedlyextruding the flat plate from a die of the extrusion machine whileheating the vessel.

[0056] The PLLA plate for fixing the artificial vertebra of the presentinvention keeps its original configuration for at least 24 weeks afterit is implanted in a living body. The PLLA plate should be graduallydecomposed to prevent surrounding cells from being damaged due to theacidification of pH caused when the plate is decomposed and absorbed ina living body. From this point of view, the PLLA plate of the presentinvention is a desirable material.

[0057] The PLLA plate of the present invention has a sufficient strengthto prevent the artificial vertebra from dropping off after implantationand firmly join to a vertebral body serving as an implant bed.Particularly in anterior fusion of the human cervical spine receiving avertical load, a plate for supporting an artificial vertebra implantedin a cervical vertebral body is essentially required to have a highstrength. The PLLA plate of the present invention has a sufficientstrength capable of withstanding such a load. In addition, the PLLAplate is superior to a metal plate in that the time-period allowing theplate to be absorbed in a living body can be controlled by adjusting itsproduction conditions.

[0058] When the artificial vertebra of the present invention isimplanted under the skin, the surface of the HAp/Col composite body issegmentalized by the infiltration of phagocytes, and the segmentationwill continue even after 24 weeks. The infiltration of phagocytes isconsidered as the same reaction as that to be caused after implantationof a collagen sponge or a collagen membrane. This reaction is differentfrom a rejection symptom in that it involves neither the mobilization ofgranulocyte nor the emergence of lymphocyte.

[0059] According to a test in which a peg is inserted into an apertureperforated in a radius/ulna of a dog, an HE-stained sample of theHAp/Col composite body implanted in the aperture suggests that theHAp/Col composite body can be joined directly to a bone. Atransformation zone observed in the boundary region between the HAp/Colcomposite body and a new bone in a Villanueva-stained sample isconsidered as a portion of the surface of the HAp/Col composite body inwhich HAp is deposited.

[0060] The phenomenons that osteoclasts emerge in the Howship'slacunae-like structure formed in the surface of the HAp/Col compositebody and that osteoblasts are arranged in the boundary region betweenthe HAp/Col composite body and a new bone could beenzyme-histochemically proved. Thus, it is believed that the HAp/Colcomposite body is an excellent biomedical material capable of inducingosteogenic cells to form a bone-remodeling unit.

BRIEF DESCRIPTION OF THE DRAWINGS

[0061]FIG. 1 shows the configuration of an artificial vertebra forhumans in Example-1 of the present invention, wherein FIG. 1(a) is a topplan view, FIG. 1(b) being a front view, and FIG. 1(c) being a sideview.

[0062]FIG. 2 is a front view showing the state after the artificialvertebra in FIG. 1 is fixed to human cervical spine by a support plate.

[0063]FIG. 3 is a side view showing the state after the artificialvertebra in FIG. 1 is fixed to human cervical spine by a support plate.

[0064]FIG. 4 is photographs showing a TEM image (scale bar: 1 μm) and anelectron diffraction image of a HAp/Col composite material.

[0065]FIG. 5 shows the configuration of an artificial vertebra inExample-3, wherein FIG. 5(a) is a top plan view, and FIG. 5(b) is a sideview.

DESCRIPTION OF THE PREFERRED EMBODIMENT

[0066] An artificial vertebra of the present invention comprises ahydroxyapatite (HAp)/collagen (Col) composite body. In production of theHAp/Col composite body, a calcium-hydroxide suspension and aphosphoric-acid solution including collagen are first prepared, and thetwo solutions are simultaneously dropped into a reaction chambercontaining distilled water by using a tube pump to form a coprecipitateor synthesize a HAp/Col composite. Then, the obtained coprecipitate isfiltered and rinsed. At this stage, the percentage of water content isin the range of about 5 to 50%. The coprecipitate is pressure-dehydratedthrough a cold isostatic pressing (CIP) method, preferably at pH 8, at atemperature of 40° C. under a pressure of 200 MPa. As a result, aHAp/Col composite body having a submicron-order pore size and a porosityranging from about 10 to 68% depending on the percentage of watercontent is obtained.

[0067] In the obtained HAp/Col composite body, a primary particle size(approximately equal to a crystallite size) of HAp is about 50 nm, and asecondary particle (a fibrous composite) has a maximum length of about20 μm and a width of about 0.5 to 1 μm, on average. The HAp/Colcomposite body can be arranged to have a three-point flexural strengthof about 38 to 45 MPa, and a Young's modulus of about 2 to 3 GPa. TheYoung's modulus of living bone is varied depending on regions, anddistributed in the range of 4 to 30 GPa. Optimally, the HAp/Colcomposite body should have a Young's modulus approximate to that ofnatural bone. While a conventional ceramics is brittle and fractural dueto its extremely high Young's modulus, the HAp/Col composite body can bereadily prepared to have various Young's moduluses ranging from that ofa soft living bone to a hard living bone. A higher Young's modulusprovides higher brittleness, and a smatter Young's modulus provideshigher softness. If a chemical cross-linking method is performed tointroduce a cross-link in collagen simultaneously with thecoprecipitation in the process of synthesizing the HAp/Col composite,the following method may be preferably used. It is understood that thecross-linking method for use in the present invention is not limited tothe chemical cross-linking method, but any other suitable cross-linkingmethod such as a thermal cross-linking or ultraviolet cross-linkingmethod may be used.

[0068] In a cross-linking method using glutalaldehyde (GA), GA is firstadded into the Ca(OH)₂ suspension (at a concentration of 1 wt % relativeto collagen). The color of the sample is changed to yellow by adding GA.During the simultaneous dropping process, a cross-linking reaction tocollagen is caused by GA before a self-organizing structure of collagenand apatite is stably established.

[0069] Specifically, the formation of the self-organizing structurewould be hindered by reason that the reaction between GA and a lysineresidue serving as a cross-linking point in collagen takes precedence.While no addition of GA causes the phenomenon that decalcified collagenis dispersed over the phosphoric-acid solution, the addition of GAallows the decalcified collagen to be agglutinated in thephosphoric-acid solution or even in a hydrochloric-acid solution,without dispersion. Considering this phenomenon, it is believed that theaddition of GA causes introduction of cross-link in collagen of thecomposite, and the cross-linked collagen gives rise to the coloring ofthe sample.

[0070] According to a transmission electron microscope image of aHAp/Col composite with a nanostructure synthesized by adding GA, afibrous structure is macroscopically observed. In microscopicalobservation, a number of short fibers each formed of a composite ofapatite and collagen are connected with each other to form a membranousstructure. As apparent from this image, the cross-linking treatmentsuppresses the formation of the self-organizing structure in whichapatite crystals are conjugated onto a collagen fiber even under asuitable condition for the self-organization of the HAp/Col composite.

[0071] The respective amounts of water and collagen in the HAp/Colcomposite body are determined through thermal analysis. The HAp/Colcomposite body subjected to a cross-linking treatment can have enhancedflexural strength, specifically a maximum flexural strength of 60 MPa.The cross-linking treatment using GA improves a material defect suchthat the surface of the HAp/Col composite body is swelled in a shorttime-period to provide enhanced material stability and improvedoperationality of the artificial vertebra during implantation.

[0072] When it is required to accelerate early bone formation becausethe artificial vertebra is implanted in a load-bearing region, a methodof impregnating the HAp/Col composite body with rhBPM-2 may beeffectively used. In this case, the concentration of rhBPM-2 ispreferably 400 μg/ml or more.

[0073] If the artificial vertebra is used for humans, the HAp/Colcomposite body is formed as a block, for example, having a horseshoeshape in a section orthogonal to the long axis thereof. Preferably, aportion of the block to be located frontward relative to the front sideof a human body has a curved surface, and a portion of the block to beinserted into vertebral bodies has rectangular planer surfaces toprovide an increased contact area with the vertebral bodies. For thispurpose, the HAp/Col composite body may be shaped as shown in FIG. 1 byusing a computer controlled drilling machine. Several HAp/Col compositebodies may be prepared to have a width W1 of about 15 mm, a depth D ofabout 10 mm, and a length L1 of 10 to 40 mm, wherein each of the HAp/Colcomposite bodies has a different length by 5 mm.

[0074] Then, a Haversian canal-like aperture having a diameter of about0.5 mm was perforated in the direction of the long axis of the blockusing a drilling machine. As shown in FIG. 1, a plural number of theapertures are arranged at even intervals in cross-section. Further, aplurality of Volkmann's canal-like apertures each having a diameter ofabout 0.5 mm are perforated in the frontward/rearward direction andrightward/leftward direction of the block. Preferably, the number ofthese apertures is arranged as much as possible depending on thestrength of the HAp/Col composite body.

[0075] Generally, a flat plate produced simply by injection-moldingpolylactic acid (PLLA) has mechanical characteristics, such as aflexural strength of about 77 MPa, a flexural modulus of about 3.3 Gpa,and a tensile strength of about 67 MPa. A published flexural strength ofcortical bone is in the range of 100 to 200 MPa. Thus, considering thestrength reduction due to hydrolysis in a living body, theinjection-molded PLLA plate has an insufficient mechanical strength as asupport for fixing an artificial vertebra.

[0076] While an injection-molded piece can be extended through a rollingprocess to improved strength, the diameter of the piece is more reducedas the draw ratio is increased, and a final product will be hardlymachined. Otherwise, an injection-molded plat plate can beextrusion-molded in such a manner that molecules are crystallized whileorienting in a uniaxial direction, to provide enhanced mechanicalcharacteristics at approximately double value, specifically a flexuralstrength of about 180 MPa, and a flexural modulus of about 6 Gpa. Aflexural strength test herein was performed according to JISK-71717.Preferably, the PLLA plate has four corner regions each formed with ascrew-insertion hole perforated in an oblique direction to prevent ascrew screwed into a vertebral body from loosening and escaping.

PRODUCTION EXAMPLE-1 Production Example of HAp/Col Composite Body

[0077] 199.1 mmol of calcium hydroxide was added into 2 dm³ of distilledwater, and the solution was stirred to keep it as a homogeneoussuspension. 59.7 mM of phosphoric-acid solution including 5 g ofpig-skin-derived atelocollagen was also prepared. These two solutionswere simultaneously dropped into a reaction vessel containing 1 dm³ ofdistilled water by using a tube pump. In this synthesizing process, themixed solution in the reaction vessel was controlled at pH 8 by a pHcontroller. Further, the temperature of the mixed solution wascontrolled at 40° C. while immersing the reaction vessel into a waterbath. A formed precipitate was filtered through a glass filter andrinsed. Then, the precipitate was pressure-dehydrated under 200 MPa for15 hours through a CIP method to form a HAp/Col composite body.

[0078] The HAp/Col composite body in the form of a block had a watercontent of about 10% and a porosity of about 20%, and the weight ratioof HAp to collagen was 80/20 (wt %). The block was immersed into anddispersed over distilled water, and then the dispersed composite wasscooped on a micro-grid covered by a collodion film to prepare a samplefor a transmission electron microscope (TEM). After electron microscopeobservation, the sample was subjected to electron diffraction. The pHand temperature in the synthesizing process could be controlled to allowthe HAp/Col composite body to have a nanocomposite structure analogousto that of natural bone, in which HAp is localized around a collagenfiber while aligned the c-axis of HAp orients along a Col fiber having alength ranging from several μm to 10 μm.

[0079] The HAp/Col composite body was cut into a block of 20×5×3 mm³,and the block was subjected to a three-point flexural test under theconditions of a crosshead speed of 0.5 mm/min, and a span of 15 mm. Inthis test result, a three-point flexural strength was 39.5±0.88 MPa, andYoung's modulus was 2.5±0.38 GPa.

TEST EXAMPLE-1 Biocompatibility Test of HAp/Col Composite Body

[0080] The HAp/Col composite body produced in the above ProductionExample was cut into blocks as samples each having a size of 4×4×1 mm³,and implanted in the dorsal regions of fifteen Wister rats,respectively. After 2, 4, 8. 12 and 24 weeks since implantation, theimplanted samples were extracted. Each of the extracted samples was cutinto two exact halves. One was used as a toluidine-blue-stained samplefor an optical microscope and a sample for a TEM, and the other was usedas a sample for a scanning electron microscope (SEM). The peripheralsurface of the HAp/Col composite block after 2 to 4 weeks sinceimplantation was infiltrated with a number of cells each having a roundnuclei.

[0081] After 4 weeks, the surface of the HAp/Col composite block wassegmented, and fibrous tissues intruded into cracks created in thesegmented surface. From the TEM observation, it was confirmed that thesecell are phagocytes phagocytizing the debris of the HAp/Col compositeblock. The peripheral surface of the HAp/Col composite block included asmall number of fibroblasts. After 12 weeks, the peripheral surface ofthe HAp/Col composite block was formed with a number of new bloodvessels. Even after 24 weeks, the HAp/Col composite block was kept in ablock shape, and phagocytes were still observed therein while the numberthereof was reduced as compared to that at the early stage afterimplantation.

TEST EXAMPLE-2 Evaluation on Bone-Conduction Ability of HAp/ColComposite Body

[0082] A bullet-shaped block (5×5×10 mm³), so-called peg, comprising theHAp/Col composite body was prepared, and each of the surfaces of theblock was formed with four drilled apertures each having a diameter of0.5 mm. Then, three of the block were immersed, respectively, intorhBPM-2 solutions of 0 μg/ml, 200 μg/ml and 400 μg/ml, and deaeratedwith a reversed air pump to allow the respective solutions to becompletely impregnated therein.

[0083] These three kinds of blocks different in impregnated rhBMP amountwere implanted, respectively, in three apertures of 6 mm diameterdrilled in the bilateral radiuses or ulnas of each of five beagles ateven intervals. As a comparative example, three apertures were simplydrilled in the radiuses or ulnas of another one beagle.

[0084] X-ray photographs were taken from three beagles including thecomparative example weekly for 12 weeks after implantation to comparerespective time-periods required for concrescence of the block to thebone. The blocks were extracted from two beagles after 8 weeks sinceimplantation, and from four beagles including the comparative exampleafter 12 weeks, to prepare 1) decalcified HE-stained samples, 2) ALP,TRAP enzyme histochemistry, and 3) non-decalcified Villanueva-stainedsamples. Optical microscope photographs were also taken from theHE-stained samples prepared after 12 weeks to measure the occupationratio (% bone area) of new bone created on the surface of the compositeblock by using Macintosh computer software (NIH image). Further, thethickness of the new bone created on the surface of the composite blockwas measured at three points, and the average value of the measuredthicknesses was determined.

[0085] In the group of the blocks using rhBMP, callus was formed aftertwo weeks since implantation in all cases. In the group of the blocksusing no rhBMP, the formation of callus was poor, but observed after 4weeks since implantation in all cases. It was judged that synostosis isachieved on X-ray photographs when any radiolucent image in the boundaryregion between the peg and the bone disappears, and the shading ishomogenized. The synostosis in the group of the blocks having theimpregnated rhBMP of 400 μg/ml was achieved significantly earlier thanthe group of 0 μg/ml. After 8 weeks since implantation, the compositeblock was joined directly to new bone having a secondary osteon(Haversian system), and non-calcified regions were scattered. Aresorption-lacunae-like structure was formed on the surface of thecomposite block, and multinucleates were observed thereon.Spindle-shaped cells are arranged in the boundary region between thecomposite block and the bone. According to Villanueva staining, thepresence of a transformation zone was found between new bone and thecomposite block. A number of cells existed on the side of the new bonein the transformation zone.

[0086] The spindle-shaped cells were positively stained by ALP staining.This suggests that these cells are osteoblasts. Not only multinucleatesin the resorption lacunae existing in the secondary osteon (Haversiansystem) but also multinucleates in the resorption-lacunae-like structureformed in the transformation zone were positively stained by TRAPstaining. This suggests that these cells are osteoclasts. While nosignificant difference in the occupation ratio (% bone area) of new bonewas confirmed between the composite blocks, the new bone was formed inthe surfaces of the composite blocks having the impregnated rhBMP of 400μg/ml at a thickness significantly greater than that in the surfaces ofthe composite blocks of 0 μg/ml.

[0087] The HAp/Col composite block had a bone-like structure in whicheach of the c-axes of HAp crystals aligned along a collagen fiber. TheHAp/Col composite block implanted under the skin was segmented, andinfiltrated with macrophages for phagocytizing the segmented composite.The HE-stained sample of the HAp/Col composite block implanted in theaperture of the bone suggests that the HAp/Col composite body can bejoined direct to natural bone. The phenomenons that osteoclasts emergein the Howship's lacunae-like structure created in the surface theHAp/Col composite body and that that osteoblasts are arranged in theboundary region between the HAp/Col composite body and a new bone couldbe enzyme-histochemically proved.

[0088] In the test where the HAp/Col composite blocks were implanted inthe apertures of the bone, the time-period required for synostosis inthe group of 400 μg/ml was significantly shorter than that in the groupof 0 μg/ml, and new bone was significantly thickly formed in thesurfaces of the HAp/Col composite blocks. While the group of 400 μg/mlshows a tendency to have a higher occupation ratio (% bone area) of newbone than that of other groups, there was no significant differencebetween the group of 0 μg/ml and the group of 200 μg/ml.

TEST EXAMPLE-3 Evaluation on Influence of BMP Impregnation in Implantingin Load-Bearing Region

[0089] In a long-tube-shaped implant formed of the HAp/Col composite tofilling a bone-defect area, the influence of the presence of theimpregnated BMP in the implant implanted in a load-bearing region on theconnection in the boundary with bone and the bone-conduction/inductionwas comparatively studied.

[0090] The HAp/Col composite body produced in Production Example-1 wassubjected to a surface cross-linking treatment using glutalaldehyde toprepare a tibia implant. The HAp/Col composite body used for the implantwas increased in cross-link number and improved in orientation ofcollagen to have an enhanced three-point flexural strength of 60 MPa.

[0091] As shown in FIG. 5, one aperture H1 having a diameter d1 of 3 mmwas drilled at the center in the long axis of the columnar implant Ihaving a diameter W1 of 15 mm and a length L1 of 20 mm, and eightapertures H2 each having a diameter d2 of 1 mm were drilled radiallyaround the aperture H1. Twelve apertures each having a diameter d3 of 1mm were also drilled from the side surface of the implant I. The implantwas implanted in the right tibia of each of three beagles. Further, theimplant was impregnated with 400 μg/ml of BMP under a negative pressure,and this implant was implanted in the right tibia of each of twobeagles. The periosteum around the implant was completely removed, andthe implant was fixed to the tibia using an Ilizarov external fixator.

[0092] After 12 weeks, a sample was collected from one of the beagles ineach of the BMP(+) group and the BMP (−) group. The external fixators oftwo beagles in the BMP(+) group were removed after 12 weeks to fullyapply a load to the implants of the two beagles. After 24 weeks, asample was collected from each of the two beagles.

[0093] A load was applied to the BMP (−) group under the fixture usingthe external fixator, and a sample was collected after 18 and 24 weeks.After implantation, X-ray photographs were taken to determine the statusof bone-formation/synostosis. Respective bone densities beforeimplantation and at sampling were also measured through a DXA method tocompare the amount of bone formation around the implant. DecalcifiedHE-stained samples and Villanueva-stained samples were prepared from thecollected samples to observe the connection with the bone in theboundary region between the implant and the bone and measure the amountof new bone created in the drilled apertures of the implant.

[0094] The average value of BMD was 2.596±0.099 g/cm² beforeimplantation, 2.551 g/cm² in the BMP (−) group after 12 weeks, 2.566g/cm² in the BMP (+) group after 12 weeks, 2.335 g/cm² in the BMP (−)group after 24 weeks, and 2.186 g/cm² in the BMP (+) group after 24weeks.

[0095] On X-ray photographs, while the BMP (−) group was poor in callusformation around the implant, synostosis was achieved in the boundaryregion between the implant and the bone at least after 12 weeks. Inbone-cut samples, the boundary region between the implant and the bonealso coalesced completely after 12 weeks. However, while some implantsexhibited the segmentation of the HAp/Col composite body and the boneformation in the central region thereof, other implants were kept in theoriginal configuration at implantation. According to the HE andVillanueva-stained samples, the HAp/Col composite body was joineddirectly to new bone. Further, a resorption-lacunae-like structure wasformed to extend to the inside of the implant.

[0096] In the surface of the composite body, multinucleates wereobserved at the resorption-lacunae formed in the boundary region betweenthe implant and the bone, and spindle-shaped cells were arranged on thesurface of the bone. This shows that the HAp/Col composite body takes abone connection form analogous to a bone-remodeling unit in whichosteoclasts absorb the composite body, and osteoblasts add new bone. Asseen in the phenomenon that a cartilage column was formed depending onregions, a bore formation form considered as endochondral ossificationwas also observed

[0097] In the BMP (+) group on X-ray photographs, callus was formed towrap around the entire peripheral surface of the implant. After 12weeks, the HAp/Col composite body completely coalesced with the bone,and a medullary cavity was formed. The HAp/Col composite body was leftin an island shape on the outside of cortical bone. After 24 weeks, thematuration of the new bone was observed from the tendency of reductionin external calcification and the highlighted image of hardening in thecortical bone region.

[0098] In bone-cut samples, the segmented HAp/Col composite bodies wereleft in an island shape within the cortical bone. After 24, a maturedbone was formed in the inside of the implant as well as the entireperipheral surface thereof. A medullary-cavity-like structure wasobserved in the central region of the implant. In tissue samples, it wasverified that the HAp/Col composite body is joined directly to naturalbone. The formation of cartilage column was observer only at a part ofthe implant.

TEST EXAMPLE-4 Implantation in Cervical Spine of Dog

[0099] The HAp/Col composite body produced in Production Example-1 wasshaped into a block of 5×5×10 mm³. Under a negative pressure, one groupof non-cross-linked artificial vertebrae were impregnated with 0 μg/mlof BMP (hereinafter referred to as “0 μg/ml group”), and the other groupof non-cross-linked artificial vertebrae were impregnated with 400 μg/mlof BMP(hereinafter referred to as “400 μg/ml group”). A PLLA plate foruse in preventing escape of the artificial vertebrae was fixed withtitanium screws. Two apertures were drilled, respectively, at distal andproximal positions of the plate, and the screws are inserted into thecorresponding apertures in an oblique direction. The artificial vertebraof the 0 μg/ml group were implanted in each of eight beagles, and theartificial vertebra of the 400 μg/ml group were implanted in each ofthree beagles.

[0100] The cervical spine of the beagle was developed from the front ofthe body. Then, a groove slightly lager than the artificial vertebraewas cut between C3 and C4, or C4 and C5 to perform the fusion of oneintervertebra and two vertebral bodies. The periosteum on the frontwardof the vertebral body was completely peeled. As with Test Example-1, theperformance after implantation was evaluated in accordance with X-rayphotographs and tissue observations. Samples of the 0 μg/ml group werecollected from four, two and two beagles, respectively, after 12, 16 and24 weeks. Samples of the 400 μg/ml group were collected from one, oneand one beagle, respectively, after 12, 16 and 24 weeks. Afterimplantation, X-ray photographs were taken monthly to evaluate thestatus of bone-formation/synostosis around the artificial vertebra. Thecollected samples were histologically evaluated.

[0101] According to test results, while the 0 μg/ml group was poor incallus formation, synostosis was achieved in the boundary region betweenthe artificial vertebra and the bone at least after 12 weeks. In the 400μg/ml group, callus was significantly formed, and callus emerged in thefrontward of the artificial vertebra. After 12 weeks or more sinceimplantation, a thick new bone was formed in the frontward of theartificial vertebra.

[0102] According to bone-cut samples, the composite body of the 0 μg/mlgroup was joined directly to new bone without existence of any softtissue between the artificial vertebra and the vertebral body. The PLLAplate was kept in the original configuration. After 12 weeks, theartificial vertebra was progressively absorbed, and hardly discriminatedfrom the surrounding vertebral bodies. In the 400 μg/ml group, a thickcortical bone was formed in the frontward of the artificial vertebra.

[0103] According to tissue samples, HE-stained samples after 12 weeksshowed that the artificial vertebra is joined directly to new bone, andthe observation result was fundamentally the same as that in theaforementioned implantation in tibia. In the surface of the compositebody, multinucleates were observed at the resorption-lacunae formed inthe boundary region between the artificial vertebra and the bone, andspindle-shaped cells were arranged on the surface of the bone to formthe bone-remodeling unit.

TEST EXAMPLE-5 Implantation in Cervical Spine of Monkey

[0104] As with Test Example-4, a columnar artificial vertebra having adiameter of 4 mm and a height of 5 mm was produced, and degassed to suckrhBMP-2 (0 mg/ml, 1 mg/ml) therein. Then, the artificial vertebra wasimplanted between C4 and C5 of the cervical spine of each of eightJapanese monkeys, and fixed by the same PLLA plate as that in TestExample-4. X-ray photographs and CT images were taken afterimplantation, and samples were collected for 3 months to performhistologic evaluations as with Test Example-4. All results of imageobservation and tissue images were the same as those obtained in theaforementioned 0 μg/ml and 400 μg/ml groups.

EMBODIMENT Embodiment-1

[0105] An artificial vertebra for humans was produced by using theHAp/Col composite body in Production Example-1. FIG. 1 shows theconfiguration of the artificial vertebra, wherein FIG. 1(a) is a topplan view, FIG. 1(b) being a front view, and FIG. 1(c) being a sideview. FIG. 2 is a schematic front view showing the state after theartificial vertebra in FIG. 1 is fixed to human cervical spine by asupport plate. FIG. 3 is a partial sectional side view showing the stateafter the artificial vertebra in FIG. 1 is fixed to human cervical spineby a support plate.

[0106] As shown in FIG. 1, a cervical-spin artificial vertebra Icomprises a horseshoe-shaped block having a depth D of 10 mm, a width W1of 15 mm, and a length L1 of 20 mm. The artificial vertebra I has sixapertures each having a diameter d1 of 0.5 mm. The apertures are drilledin the long axis of the block at even intervals. Further, nine aperturesH2 each having a diameter d2 of 0.5 mm are drilled in theforward/rearward direction of the block, and six apertures H3 eachhaving a diameter d3 of 0.5 mm are drilled in the rightward/leftwarddirection of the block. A polylactic-acid (PLLA) support plate P forfixing the artificial vertebra is produced by injection-molding moltenpolylactic acid and extrusion-molding the injection-molded product insuch a manner that molecules are crystallized while orienting in auniaxial direction. The PLLA plate P has a length L2 of 25 mm, a widthW2 of 10 mm and a thickness T of 2 mm. As shown in FIGS. 2 and 3, eachof the four corner regions of the PLLA plate P is formed with ascrew-insertion aperture H4 having a diameter of 4 mm. The aperture H4is drilled in an oblique direction to prevent a screw S inserted thereinfrom loosening. The screw S is made of titanium. The screw S is screwedinto the vertebral bones C3 and C4 through the aperture H4 to fix thePLLA plate P and the block as shown in FIG. 3.

INDUSTRIAL APPLICABILITY

[0107] As mentioned above, the artificial vertebra of the presentinvention comprising a HAp/Col composite body prepared through acoprecipitation process and having a self-organizing function is abiomedical material having a bone-remodeling unit and a bone-conductionability equivalent to an allogeneic bone. The artificial vertebra addedwith an osteogenic factor such as BMP can form new bone in the entireperipheral surface under a load at earlier stage after implantation andaccelerate the transformation of the new bone to matured bone.

[0108] There has been no report describing that an artificial vertebraimplanted in the cervical spine receiving a vertical load as in dogs ormonkeys. The artificial vertebra of the present invention can achievehuman's cervical spine fusion using a bioabsorbable material capable ofbeing transformed to an autologous bone. Thus, the artificial vertebraof the present invention greatly contributes to reparative surgeries fora bone defect area of a vertebral body.

What is claimed is:
 1. An artificial vertebra system having abone-marrow regenerating function, comprising a hydroxyapatite(HAp)/collagen (Col) composite body formed by pressure-dehydrating acoprecipitate of hydroxyapatite and collagen to have a nanocompositestructure in which HAp particles are conjugated along a Col fiber whilealigned each of the c-axes of said HAp particles along said Col fiber,said HAp/Col composite body being formed with a perforated aperture forallowing a blood vessel and an osteogenic cell to migrate thereinto. 2.The artificial vertebra as defined in claim 1, wherein the weight ratioof HAp to Col in said HAp/Col composite body is in the range of 70:30 to80:20 which is equivalent to that of a bone.
 3. The artificial vertebraas defined in claim 1 or 2, wherein said coprecipitate has across-linked surface.
 4. The artificial vertebra as defined in eitherone of claims 1 to 3, wherein said HAp/Col composite body is formed as ablock having a horseshoe shape in a section orthogonal to the long axisthereof, wherein a portion of said block to be located frontwardrelative to the front side of a human body has a curved surface havingan analogous shape to that of a vertebral body, and a portion of saidblock to be inserted into vertebral bodies has rectangular planersurfaces to provide an increased contact area with the vertebral bodies.5. The artificial vertebra as defined in either one of claims 1 to 4,wherein said aperture is perforated in the direction of the long axis ofsaid HAp/Col composite body in a configuration analogous to that of aHaversian canal, wherein a plural number of said apertures are arrangedat even intervals.
 6. The artificial vertebra as defined in either oneof claims 1 to 5, wherein said aperture is perforated in thefrontward/rearward direction and rightward/leftward direction relativeto the front side of a human body in a configuration analogous to thatof a Volkmann's canal, wherein a plural number of said apertures arearranged at even intervals.
 7. The artificial vertebra as defined ineither one of claims 1 to 6, wherein said HAp/Col composite body isadapted to receive a load in an early stage after implantation, whereinsaid HAp/Col composite body has a function of being transformed into anautologous bone in such a manner that new bone (bone marrow) isinitially formed in said perforated aperture and the transformation isthen extended from said new bone region to the periphery thereof.
 8. Theartificial vertebra as defined in either one of claims 1 to 7, whichincludes an osteogenic factor impregnated into said HAp/Col compositebody.
 9. A biodecomposable/bioabsorbable support for fixing anartificial vertebra, comprising a polylactic acid plate prepared byinjection-molding molten polylactic acid and then extrusion-molding saidinjection-molded polylactic acid in such a manner that it isdraw-oriented in a uniaxial direction, said plate having four cornerregions each formed with a screw hole for fixing said plate to vertebralbodies.
 10. The biodecomposable/bioabsorbable support as defined inclaim 9, wherein said screw hole is perforated in an oblique direction.11. An artificial vertebra assembly comprising in combination theartificial vertebra as defined in either one of claims 1 to 8, and thebiodecomposable/bioabsorbable support as defined in claim 9 or 10.